Promoter nucleosome dynamics regulated by signaling through the CTD code

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand  Is a corresponding author
  1. University of Namur, Belgium
  2. LSU Health Sciences Center, United States
  3. Universidad de Salamanca, Spain
  4. Universitat Pompeu Fabra, Spain

Abstract

The phosphorylation of the RNA polymerase II CTD plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phosphoS2 CTD nearby the promoter impairs the phosphoS5 CTD dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phosphoS2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signaling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signaling through the CTD code regulates promoter nucleosomes dynamics.

Article and author information

Author details

  1. Philippe Materne

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Jayamani Anandhakumar

    Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Valerie Migeot

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Ignacio Soriano

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Carlo Yague-Sanz

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Elena Hidalgo

    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Carole Mignion

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Luis Quintales

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Francisco Antequera

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Damien Hermand

    Namur Research College, University of Namur, Namur, Belgium
    For correspondence
    Damien.Hermand@unamur.be
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Materne et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,705
    views
  • 643
    downloads
  • 20
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand
(2015)
Promoter nucleosome dynamics regulated by signaling through the CTD code
eLife 4:e09008.
https://doi.org/10.7554/eLife.09008

Share this article

https://doi.org/10.7554/eLife.09008

Further reading

    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease
    Maruti Nandan Rai, Qing Lan ... Koon Ho Wong
    Research Article Updated

    Candida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects fluconazole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabrata’s survival in macrophages and drug tolerance.

    1. Chromosomes and Gene Expression
    2. Neuroscience
    Robyn D Moir, Emilio Merheb ... Ian M Willis
    Research Article

    Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of Polr3-related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of Polr3-related disease pathogenesis is unknown. We developed a postnatal whole-body mouse model expressing pathogenic Polr3a mutations to examine the molecular mechanisms by which reduced Pol III transcription results primarily in central nervous system phenotypes. Polr3a mutant mice exhibit behavioral deficits, cerebral pathology and exocrine pancreatic atrophy. Transcriptome and immunohistochemistry analyses of cerebra during disease progression show a reduction in most Pol III transcripts, induction of innate immune and integrated stress responses and cell-type-specific gene expression changes reflecting neuron and oligodendrocyte loss and microglial activation. Earlier in the disease when integrated stress and innate immune responses are minimally induced, mature tRNA sequencing revealed a global reduction in tRNA levels and an altered tRNA profile but no changes in other Pol III transcripts. Thus, changes in the size and/or composition of the tRNA pool have a causal role in disease initiation. Our findings reveal different tissue- and brain region-specific sensitivities to a defect in Pol III transcription.